Germicidal compositions



United States Patent 3,103,036 GERMECKDAL COMPOSITIONS Nicholas M. Molnar, New York, N.Y., assignor to Fine Organics, Ina, Lodi, N.J., a corporation of New York No Drawing. Filed Nov. 12, 1959, Ser. No. 852,172 4 Claims. (Cl. 167-22) This invention relates to novel synergistic combinations of germicides. The compositions are useful for the treatment of animate and inanimate surfaces for the express purpose of inhibiting or destroying a broad spectrum of undesirable microorganisms, e.g., bacterial, fungi and yeasts.

The vast majority of sanitizers, antiseptics and disinfectants in use today for treatment of fabrics, hard surfaces (walls, floors, instruments, etc.), skin, body orifices and scalp, fall into two major classes, viz., those that are phenolic in nature and those formulated with quaternary ammonium compounds.

The phenolic substances are anionic in nature, and as is well known, are effective at low concentrations against gram-positive bacteria. However, they show poor action against gram-negative bacteria and other microorganisms. The quaternary ammonium compounds which belong to the class of cationic germicides, in addition to being effective against gram-positive bacteria, also possess activity against gram-negative organisms. the outstanding features of phenolics, on the one hand, and quaternary ammonium compounds, on the other, cannot be combined. Mixtures of those two classes of germicides mutually inactivate each other and, in consequence, the mixtures are ineffectual as germicides.

It is among the principal objects of this invention to provide effective combinations of anionic germicides and cationic germicides, but not of the quaternary ammonium type, which not only do not inactivate each other, but on the contrary, are synergistic in action. The antimicrobial activity of the novel compositions is far greater than that contributed by either component alone at levels equal to that present in the combination.

It is a further object of this invention to set forth practical areas of utility for the novel germicidal combinations, as for example, in the treatment of textiles and hard surfaces.

Other objects and advantages of the invention, such as in formulating the novel germicidal compositions for use in skin care, hair and scalp, will be apparent from the following description of the invention.

Cationic compounds which combine with gerrnicidally active anionic compounds to form the compositions of this invention that provide synergistic antimicrobial action are as follows:

(1) N-alkylated or alkenylated alkylene polyamines which possess at least one of said aliphatic hydrocarbon groups having from 6 to 20 carbon atoms joined to one of the amino nitrogen groups and having one to live alkylene groups interconnected by nitrogen atoms. They may be represented structurally in their simpler form as follows:

in which R is an alkylene radical which may be the ethylene radical (--CH CH the isopropylene radical [CH Cl-I(CH the trimethylene radical or a mixture of such radicals and n may be Zero, in which case the parenthesized group is non-existent or It may be a whole number from *1 to 4; and X is an alkyl or alkenyl radical which may have from one to twenty carbon atoms, e.-g., in the alkyls in the range from methyl to eicosyl (C l-I and Y and Y are hydro- It is well known that.

3,1h8dl36 Patented Oct. 22, 1963 ice gen atoms or alkyl or alkenyl or carboxyalkyl or carboxy alkenyl groups having from 1 to 20 carbon atoms in the aliphatic hydrocarbon radical.

(2) Acylamidoalkylene polyamines wherein the acyl group has from 2 to 20 carbon atoms joined through the carbonyl group to one of the amino nitrogen groups and having one to five alkylene groups interconnected by nitrogen atoms. They may be represented structurally in their simpler form as follows:

X(l?--NH-R- (NHR) NY1Yz in which the symbols X, R, Y, and Y and n have the same meaning as defined in the aforementioned N-alkylated or alkeny lated alkylene polyamines.

The above-described cationic compounds, accordingly, may be represented structurally by the general formula:

wherein m is zero or one, and the symbols n, X, R, Y and Y have the above defined significance.

It will be apparent that X, and Y and Y (when aliphatic) are the aliphatic hydrocarbon radicals present in the fatty alcohols and fatty acids, i.e., either saturated or 2,2 methylene bis (3,4,6 trichlorophenol) 2,2 methylene bis (4,6 d'ichlorophenol), 2,2 methylene bis (4 chlorophenol),

2,2 thio bis (4,6 di'chlorophenol).

(3) Salicylanilides, e. g.-

Salicylanilide, Monohalogenated salicylanilides, Polyhalogenated salicylanilides.

Also included among the aforesaid anionics are halogenated carbanilides and thiocarbanilides. These diphenyl ureas and thioureas, in consequence of possible enolizations and tautomerizations, possess the anionic properties of phenols akin to those of the phenols in the above classes 1 to 3.

In addition to the synergistic activity described hereinafter, the novel anionic-cationic germicidal compositions of this invention have other desirable features as follows:

:(a) The cationic component has a solubilizing efiect on the anionic component which is generally water-insoluble. This is of practical importance because a concentrated solution of the germicides can be diluted with water to use-level without separation of the anionic fraction. Non-ionic and ampholytic detergents are compatible with the synergistic germicidal compositions and can be used as adjuncts for emulsification and cleansing purposes.

(17) Textiles treated with the germicidal systems described herein develop antistatic properties and soft feel.

(0) The germicidal compositions described herein possess excellent wetting properties and permit thorough penetration and uniform distribution of the germicidal compositions onto the surfaces under treatment.

(d) The cationic component of the cationic-anionic germicidal composition inhibits darkening of phenolic anionic component when exposed to light.

The instant cationic components and the anionic components interact chemically with each other to form the synergistic combinations. This is manifested, inter alia, by the fact that heat is evolved when the cationic substance is mixed with the anionic substance, a phenomenon indicative of an exothermic reaction. Furthermore, as mentioned in d, supra, the sensitivity of phenolics to light (manifested normally by phenolics when exposed to light) is absent in the instant phenolic-cationic combination.

The synergistic action of the novel germicide mixtures is achieved over a wide range of weight ratios of the anionic-cationic components. The preferred range, although it is not to be construed as restrictive, is 1 to 9 parts of the anionic component to 9 to 1 parts of the cationic component.

Examples of the synergistic action of the novel germicidal combinations are given in the following, embodying uses in the fields of textile sanitization, disinfection of hard surfaces, skin care, and hair and scalp treatment.

EXAMPLE 1 Textile Sanitization Fabrics (cottons, woolens and synthetic fibers) are readily treated with anionic and cationic germicides added to a special rinse water or the final rinse Water in a laundry wash cycle. Outstanding antimicrobial activity is achieved by employing the novel germicidal combinations embodied in my invention. The synergism shown by several of these germicidal compositions is illustrated in the following:

(a) Stock solutions were prepared for use in a rinse treat of bed linens. The solutions are aqueous.

1) hexachlorophene (2,2 methylene bis (3,4,6 trichlorophenoD);

(2) 5% lauryl diethylene triamine (LDT);

(3) 5% of a 1:1 mixture of hexachlorophene and LDT.

Each of the stock solutions was added to water to give 0.1, 0.25 and 0.5 dilution levels to yield 50, 125 and 250 ppm. of active germicide.

Bed linens were steeped in these solutions for 5 minutes (fabric to Water ratio was fixed at 1:10). The linens were dried and mm. discs were cut out and placed on nutrient agar plates seeded with 24 hour broth cultures of Staphylococcus aureus and Escherichia coli. The plates were incubated overnight and zones of inhibition were recorded. Results are given in Table I, as follows:

TABLE I It will be noted from Table I that the 1:1 mixture of hexachlorophene and lauryl diethylene triamine (stock solution) at levels of 0.1, 0.25 and 0.5% in water gave consistently high activity against both the gram-positive S. aureus and gram-negative E. coli. At the same concentrations, hexachlorophene alone was effective only against S. aureus, and LDT was active against the test organisms only at the 0.5% level. The unexpectedly strong activity at all levels of the germicidal mixture against E. coli, when each component failed to show activity alone, shows that synergistic activity exists between the anionic germicide hexachlorophene and the cationic germicide lauryl diethylene triamine.

Other germicidal combinations embodied in this in- 4 vention which have been investigated for their synergistic activity in the treatment of fabrics are listed below:

Lauroylamido diethylene diamine and 2,2 thiobis (4,6

dichlorophenol) Stearyl triethylene tetramine and 4',5 dibromosalicylanilide;

Dimethylamino propyl lauramide and o-benzyl-p-chlorophenol;

Dimethylamino propyl stearamide and 2,2 methylene bis (4,6 dichlorophenol);

Lauryl diethylene triamine and 3,4,4 trichlorocarbanilide;

Lauryl diethylene triamine and 3,3,4',5 tetrachlorosalicyl anilide.

The above examples of synergistic germicidal pairs gave antibacterial results in the rinse water treatment of fabrics which were similar to those described for the hexachlorophene-LDT combination.

It should be pointed out that fabrics, particularly cottons, treated with the germicidal combinations embodied in my invention are resistant to mildew and other mold spoilage. For example, Clzaetomium globosum, Aspergillus and Penicillium strains are prevented from attacking cottons, paper, paper board and other cellulosics, when the latter is given treatment with the novel germicidal mixtures.

EXAMPLE 2 Hard Surface Treatment In another embodiment the germicidal combinations manifest synergistic action on hard surfaces and show excellent kill activity under the conditions of the AOAC Use Dilution Confirmation Test, as described in the J. Assoc. Off. Agric. Chem. 36, 466 (1953).

Germicidal preparations that satisfy the requirements of the test in accordance with governmental regulations are defined as disinfectants for use on hard surfaces (walls, floors, instruments, rubber goods, etc.). The test organisms employed are Salmonella choleraesuis and Staphylococcus aureus representative of enteric and of pyogenic bacteria, respectively. The test requires that at the recommended use-dilution of the germicide preparation, complete kill of the test organism in 10 minutes or less should occur. The higher the use-dilution achieving this requirement, the more potent is the germicidal preparation.

Results given in Table II demonstrate that a 5% stock solution of a 1:1 mixture of lauryl diethylene triamine (LDT) and 3,3',4,5 itetrachlorosalicylanilide causes kill of S. choleraesuis at a dilution of 150 as compared to a dilution value of only 25 for the 5% stock solution of the tetrachlorosalicylanilide and a dilution value of for 5% LDT.

TABLE II Use-diluti0n to kill Germicidal Preparation S. aureus S. choleraesuis 5% tetraehlorosalicylanilide ('ICS) 300 25 5% lauryldiethylene triamine (LDT) 80 5% 111 mixture of T08 and LDT 350 The synergistic action of the germicidal combination against both organisms is very evident.

EXAMPLE 3 Skin and Scalp Treatment the gram-negative test organism associated with certain skin disorders. Against these two organisms I have found that minimum effective concentration to produce bacteriostasis and/or bactericidal action is lowest for germicidal mixtures described herein as compared to the action of the anionic germicide component or eationic germicide component separately. The synergistic action is demonstrated in the standard toxic dilution test which measures the minimum effective concentration of a germicidal preparation in nutrient broth which would inhibit or kill the test organism.

The germicidal combinations employed by way of illustration are various weight proportions of 4,5 dichlorosalicylanilide (DCS) and lauryldiethylene triamine (LDT) The results are given in Table III, as follows:

TABLE III p.p.m. in Nutrient Broth Seeded Germieidal Preparation S. aureus E. coli stasis kill stasis kill DGS 2 25 20 125 LD'I 4 40 4 35 1:2 mixture of DCS:LDT O. 5 4 2 15 1:1 mixture of DCS:LDT 0.25 2 1 2:1 mixture of DCS:LDT O. 5 4 2 1:9 mixture of DCS:LDT 1. 5 15 1 10 9:1 mixture of DCSzLDT 1. 0 10 3 The germicidal mixture as shown in Table III yields antibacterial activity at concentrations considerably lower than can be predicted on the basis of the known activity of the component parts.

The eflectiveness of such germicidal combinations at very low concentrations provides a practical system for the degerming of skin and scalp.

Anionic compounds of the class described above and methods of preparing them are described, inter alia, in

6 US. Patent No. 2,267,204 and German Patent No. D.B.P. 1,041,627.

Although the toregoing description of the invention and the illustrative examples set forth comprise preferred embodiments of the invention by way of showing the synergistic germicidal combinations and the possibilities of using them, it is to be understood that the invention is not limited thereby and that other combinations and end uses will be apparent without departing from the scope of the invention as defined in the appended claims.

I claim:

1. A composition comprising the combination of about 1 to 9 parts of lauryl diethylene triamine and about 9 to 1 parts of 2,2 methylene bis (3,4,6-trichlorophenol).

2. A composition comprising the combination of about 1 to 9 parts of lauryl diethy-lenetriamine and about 9 to 1 parts of 4', 5 dibromosalicylanilide.

3. A composition comprising the combination of about 9-1 parts of lauryl diethylene triamine and about 1-9 parts of polybrominated salicylanilide.

4. A composition comprising the combination of about 9-l parts of lauryl diethylene triamine and about 1-9 parts of halogenated salicylanilide.

References Cited in the file of this patent UNITED STATES PATENTS 2,244,712 Kyrides June 10, 1941 2,246,524 Kyrides June 21, 1941 2,250,480 Gump July 29, 1941 OTHER REFERENCES Hunter et al.: Am. Perf. and Essential Oil Review, vol. 61, February 1953, pp. 122-127.

U.S. Dispensatory, 25th ed., Lippincott Co., Phila., Pa. (1955), pp. 1206-7.

Wadley: The Evidence Required to Show Synergistic Action of Insecticides and a Short Cut in Analysis, US. Dept. of Agr., Bulletin ET-223, recd February 5, 1957, pp. 1-7. 

1. A COMPOSITION COMPRISING THE COMBINATION OF ABOUT 1 TO 9 PARTS OF LAURYL DIETHYLENE TRIAMINE AND ABOUT 9 TO 1 PARTS OF 2,2'' METHYLENE BIS (3,4,6-TRICHLOROPHENOL).
 4. A COMPOSITION COMPRISING THE COMBINATION OF ABOUT 9-1 PARTS OF LAURYL DIETHYLENE TRIAMINE AND ABOUT 1-9 PARTS OF HALOGENATED SALICYLANILIDE. 